Imaging synaptic neurexin-neuroligin complexes by proximity biotinylation: applications to the molecular pathogenesis of autism
Massachusetts Institute of Technology
A major underlying cause of autism is hypothesized to be defects in the development of synapses, which are the points of contact between brain cells through which brain cells communicate. During development, proteins located on the surfaces of contacting neurons physically interact to regulate the fate and function of the synapse. Two types of proteins, called neurexins and neuroligins, are examples of such synaptic proteins. Mutations in genes encoding both of these proteins have been linked to autism, and it has been hypothesized that these mutations may impair the interaction between neuroligin and neurexin at the synapse. Dr. Thyagarajan will study the molecular properties of the neurexin-neuroligin complex in live neuronal synapses. They will use techniques from chemistry, neuroscience, and molecular biology to develop a novel technology to optically image the formation, dynamics, and function of protein complexes at live synapses. They will use this technology to study neurexins and neuroligins during synapse development, and determine the effects of autism-linked mutations in these genes on the formation and functions of synapses. Insights from these studies may lead to a better understanding of the underlying biological causes of autism, and may aid in the future development of targeted therapeutic strategies.